Edward J Gane1, Kris V Kowdley2, David Pound3, Catherine A M Stedman4, Mitchell Davis5, Kyle Etzkorn6, Stuart C Gordon7, David Bernstein8, Gregory Everson9, Maribel Rodriguez-Torres10, Naoky Tsai11, Omer Khalid12, Jenny C Yang13, Sophia Lu13, Hadas Dvory-Sobol13, Luisa M Stamm13, Diana M Brainard13, John G McHutchison13, Myron Tong14, Raymond T Chung15, Kimberly Beavers16, John E Poulos17, Paul Y Kwo18, Mindie H Nguyen19. 1. Auckland Clinical Studies, Auckland, New Zealand. Electronic address: edgane@adhb.govt.nz. 2. Swedish Medical Center, Seattle, Washington. 3. Indianapolis Gastroenterology Research Foundation, Indianapolis, Indiana. 4. Christchurch Hospital and University of Otago, Christchurch, New Zealand. 5. Digestive CARE-South Florida Center of Gastroenterology, Wellington, Florida. 6. Borland-Groover Clinic, Jacksonville, Mississippi. 7. Henry Ford Hospital and Health System, Detroit, Michigan. 8. North Shore/Long Island Jewish PRIME, Manhasset, New York. 9. University of Colorado, Aurora, Colorado. 10. Fundación De Investigación De Diego, San Juan, Puerto Rico. 11. Queens Liver Center, Honolulu, Hawaii. 12. Digestive Health Specialists, Winston-Salem, North Carolina. 13. Gilead Sciences, Foster City, California. 14. Huntington Medical Research Institutes Liver Center, Pasadena, California. 15. Massachusetts General Hospital, Boston, Massachusetts. 16. Medical University of South Carolina, Charleston, South Carolina. 17. Cumberland Research Associates, LLC, Fayetteville, Georgia. 18. Indiana University School of Medicine, Indiana. 19. Stanford University Medical Center, Palo Alto, California.
Abstract
BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.
BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.
Authors: Tarik Asselah; Christophe Moreno; Christoph Sarrazin; Michael Gschwantler; Graham R Foster; Antonio Craxí; Peter Buggisch; Faisal Sanai; Ceyhun Bicer; Oliver Lenz; Gino Van Dooren; Catherine Nalpas; Isabelle Lonjon-Domanec; Michael Schlag; Maria Buti Journal: PLoS One Date: 2017-01-05 Impact factor: 3.240
Authors: Giovanni Cenderello; Caterina Fanizza; Simona Marenco; Laura Ambra Nicolini; Stefania Artioli; Isabella Baldissarro; Chiara Dentone; Pasqualina De Leo; Antonio Di Biagio Journal: Clinicoecon Outcomes Res Date: 2017-05-22
Authors: Thalia Medeiros; Camila de Morais Salviato; Natalia Fonseca do Rosário; Geórgia do Nascimento Saraiva; Eliane Bordalo Cathalá Esberard; Jorge Reis Almeida; Analúcia Rampazzo Xavier; Andrea Alice da Silva Journal: Int J Clin Pharm Date: 2017-10-27